Our objective in the proposed work is to investigate certain fundamental problems in the mineralization of bones and teeth. Our goal is to examine bone cells with particular reference to the location and nature of the mineral constituents therin. The methodology will rely mainly on electron microscopy of frozen thin-sections and freeze substitution. Matrix vesicles and dentinal globules will be studied in the same way in order to determine the presence and the form of the mineral components they may contain. Another goal is to continue with our effort at localizing the enzyme carbonic anhydrase in osteoclasts. At this time we shall attempt to demonstrate the subcellular localization using labeled inhibitor autoradiography. Finally, we propose to study bone cell modulation and bone synthesis induced by estrogen in avian species. By electron microscopy and autoradiography we will follow the changes in the responsive cell(s) from the undifferentiated to the differentiated bone synthesizing cell. Biochemical changes associated with cell differentiation and bone synthesis will be done in parallel.